Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4GPX7K)

• DOT Name: Leukocyte tyrosine kinase receptor (LTK)
• Synonyms: EC 2.7.10.1; Protein tyrosine kinase 1
• Gene Name: LTK
• UniProt ID: LTK_HUMAN
• PDB ID: 7NX0; 7NX1
• EC Number: 2.7.10.1
• Pfam ID: PF12810 ; PF07714
• Sequence:
  MGCWGQLLVWFGAAGAILCSSPGSQETFLRSSPLPLASPSPRDPKVSAPPSILEPASPLN
  SPGTEGSWLFSTCGASGRHGPTQTQCDGAYAGTSVVVTVGAAGQLRGVQLWRVPGPGQYL
  ISAYGAAGGKGAKNHLSRAHGVFVSAIFSLGLGESLYILVGQQGEDACPGGSPESQLVCL
  GESRAVEEHAAMDGSEGVPGSRRWAGGGGGGGGATYVFRVRAGELEPLLVAAGGGGRAYL
  RPRDRGRTQASPEKLENRSEAPGSGGRGGAAGGGGGWTSRAPSPQAGRSLQEGAEGGQGC
  SEAWATLGWAAAGGFGGGGGACTAGGGGGGYRGGDASETDNLWADGEDGVSFIHPSSELF
  LQPLAVTENHGEVEIRRHLNCSHCPLRDCQWQAELQLAECLCPEGMELAVDNVTCMDLHK
  PPGPLVLMVAVVATSTLSLLMVCGVLILVKQKKWQGLQEMRLPSPELELSKLRTSAIRTA
  PNPYYCQVGLGPAQSWPLPPGVTEVSPANVTLLRALGHGAFGEVYEGLVIGLPGDSSPLQ
  VAIKTLPELCSPQDELDFLMEALIISKFRHQNIVRCVGLSLRATPRLILLELMSGGDMKS
  FLRHSRPHLGQPSPLVMRDLLQLAQDIAQGCHYLEENHFIHRDIAARNCLLSCAGPSRVA
  KIGDFGMARDIYRASYYRRGDRALLPVKWMPPEAFLEGIFTSKTDSWSFGVLLWEIFSLG
  YMPYPGRTNQEVLDFVVGGGRMDPPRGCPGPVYRIMTQCWQHEPELRPSFASILERLQYC
  TQDPDVLNSLLPMELGPTPEEEGTSGLGNRSLECLRPPQPQELSPEKLKSWGGSPLGPWL
  SSGLKPLKSRGLQPQNLWNPTYRS
• Function: Receptor with a tyrosine-protein kinase activity. Following activation by ALKAL1 or ALKAL2 ligands at the cell surface, transduces an extracellular signal into an intracellular response. Ligand-binding to the extracellular domain induces tyrosine kinase activation, leading to activation of the mitogen-activated protein kinase (MAPK) pathway. Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif. The exact function of this protein is not known; studies with chimeric proteins demonstrate its ability to promote growth and specifically neurite outgrowth, and cell survival. Involved in regulation of the secretory pathway involving endoplasmic reticulum (ER) export sites (ERESs) and ER to Golgi transport.
• Tissue Specificity: Expressed in non-hematopoietic cell lines and T- and B-cell lines.

Molecular Interaction Atlas (MIA) of This DOT

4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Leukocyte tyrosine kinase receptor (LTK).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Leukocyte tyrosine kinase receptor (LTK).	[3]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Leukocyte tyrosine kinase receptor (LTK).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Leukocyte tyrosine kinase receptor (LTK).	[7]

3 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Leukocyte tyrosine kinase receptor (LTK).	[2]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Leukocyte tyrosine kinase receptor (LTK).	[4]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of Leukocyte tyrosine kinase receptor (LTK).	[6]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [3] Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood. Epigenetics. 2014 May;9(5):774-82. doi: 10.4161/epi.28153. Epub 2014 Feb 13.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [5] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [6] Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
• [7] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.